Immunological response after early extra and regular MMR immunization: 10 years follow-up
| ISRCTN | ISRCTN85713294 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN85713294 |
| Secondary identifying numbers | IIV-628 |
- Submission date
- 11/07/2023
- Registration date
- 05/10/2023
- Last edited
- 19/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
From May 2013 until March 2014, a measles epidemic occurred in the Netherlands. During this epidemic, the Dutch Ministry of Health decided to offer infants between 6 and 12 months of age, living in the measles outbreak area, an early extra MMR (MMR-0) immunization during this outbreak, to protect children below 1 year of age in areas with lower immunization coverage (less than 90%) and thus with higher risk of exposure to measles virus. Researchers previously investigated the immunological response to early vaccination in a group of these children and a control group. Blood samples were taken at 14 months, 15.5 months, 2 years, 4 years and 6-7 years of age. About 12% of the children who received MMR-0 between 6 and 8 months of age had no detectable antibodies at 14 months of age before MMR-1. All other children had MMR-0-induced antibody levels above the protective threshold and were regarded as protected against measles during the epidemic. After the regular MMR-1 vaccination at 14 months of age, all children had developed protective measles antibody levels. However, 3 years later, measles antibody levels had dropped below the protective threshold in 11% of children, particularly children who received MMR-0 between 6 and 8 months of age. At 6-7 years of age, this percentage had increased to 68%. Among the children who received MMR-0 between 9 and 12 months of age and the children of the control groups who only received their regular MMR-1 at 14 months of age, 21% and 11% had dropped below the threshold of protection, respectively.
The aim of this study is to analyse the levels of measles-specific antibodies in children who participated in the EMI study or BMR-nul-study at about 11 years of age, which is 2 years (+/- 2 months) after having received the regular MMR-2 vaccination. The proportion of children who have gained protective antibody levels through MMR-2 vaccination compared to the ones who haven’t will be assessed. Finally, the levels and the quality of antibodies will be compared between children who had received an MMR-0 at 6-12 months of age and the children of the control group who only received the regular MMR-1 vaccination at 14 months of age.
Who can participate?
Children aged 10 to 12 years who previously participated in the EMI clinical study on the immunological response after MMR-0 immunization or the epidemiological questionnaire study BMR-nul.
What does the study involve?
One blood sample is obtained by fingerstick and one short questionnaire is completed.
What are the possible benefits and risks of participating?
The children have no direct benefit from participating in the study. Blood collection will be done using a finger stick, which poses no risk.
Where is the study run from?
Dutch National Institute of Health and the Environment (RIVM) (Netherlands)
When is the study starting and how long is it expected to run for?
June 2023 to November 2024
Who is funding the study?
The Dutch Ministry of Health, Welfare and Sport (Netherlands)
Who is the main contact?
bmr-nul-emi@rivm.nl
Contact information
Principal Investigator
9 Antonie van Leeuwenhoeklaan
Bilthoven
3721MA
Netherlands
| Phone | +31 (0)886897312 |
|---|---|
| bmr-nul-emi@rivm.nl |
Study information
| Study design | Observational case-control study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Case-control study |
| Study setting(s) | Home, Internet/virtual |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Observational study on immunological response 2 years after MMR-2 vaccination in children that received early extra or regular MMR immunization as infants to assess long-term effect of early extra MMR immunization |
| Study acronym | EMI-3 |
| Study objectives | Previously the immunological response to early vaccination was investigated in a cohort of children with the last blood sample obtained at 6-7 years of age, which is 6 years after the MMR-1 vaccination (NL45616.094.13/IIV-273 and NL69434.100.19/IIV-411). A large part of the early extra MMR-0 vaccinated children had protective measles levels at the age of 14 months. However, the decline in antibody levels was steeper than in children who received the regular MMR-1 vaccination and for some children antibody levels dropped below seroprotective levels at 4 and 6-7 years of age. This study will monitor the effect of MMR-2 on these children. |
| Ethics approval(s) |
Approved 14/09/2023, Dutch Medical Ethics Committee MEC-U (Postbus 2500, Nieuwegein, 3430 EM, Netherlands; +31 (0)88 320 8784; info@mec-u.nl), ref: NL84855.100.23 (R23.050) |
| Health condition(s) or problem(s) studied | Measles immunization in children |
| Intervention | In this follow-up study, a single small blood sample will be collected by finger-stick of children who previously were immunized with an MMR-0 vaccination between 6-12 months of age and children of a control group who only received the regular MMR-1 at 14 months of age. Blood sampling through a finger-stick will be performed at 2 years (+/- 2 months) post MMR-2 vaccination. Parents can perform the finger-stick on their child themselves and mail the blood sample to the RIVM. If parents do not feel comfortable performing the finger-stick themselves, an alternative can be arranged. Furthermore, a digital questionnaire is filled out with questions about the health of the child and other vaccinations. |
| Intervention type | Other |
| Primary outcome measure | Measles-specific serum IgG measured by Luminex multiplex-based serology and virus-neutralizing antibodies by Plaque Reduction Neutralization Test (PRNT) 2 years (+/- 2 months) after MMR-2 vaccination |
| Secondary outcome measures | Serum IgG antibody concentrations against mumps and rubella measured by Luminex multiplex-based serology 2 years (+/- 2 months) after MMR-2 vaccination |
| Overall study start date | 01/06/2023 |
| Completion date | 26/11/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Child |
| Lower age limit | 10 Years |
| Upper age limit | 12 Years |
| Sex | Both |
| Target number of participants | 80 |
| Total final enrolment | 88 |
| Key inclusion criteria | Current inclusion criteria as of 30/01/2024: 1. Participation in the study on the immunological effects of early extra measles vaccination, as described in a separate study protocol (NL45616.094.13/IIV-273) or participation in the BMR-nul-study on epidemiological effects of early extra measles vaccination as described in a separate study protocol 2. The parents/legal representatives accept participation in the trial according to the described procedures 3. Presence of an informed consent signed by both parents/legal representatives 4. Children must have received the MMR-2 vaccination Previous inclusion criteria: 1. Participation in the study on the immunological effects of early extra measles vaccination, as described in a separate study protocol (NL45616.094.13/IIV-273) 2. The parents/legal representatives accept participation in the trial according to the described procedures 3. Presence of an informed consent signed by both parents/legal representatives 4. Children must have received the MMR-2 vaccination |
| Key exclusion criteria | 1. Presence of a serious disease that requires medical care that can interfere with the results of the study 2. Known or suspected immunological disorder 3. Bleeding disorders |
| Date of first enrolment | 09/10/2023 |
| Date of final enrolment | 18/07/2024 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Bilthoven
3721 MA
Netherlands
Sponsor information
Research organisation
9 Antonie van Leeuwenhoeklaan
Bilthoven
3721MA
Netherlands
| Phone | +31 (0)886894154 |
|---|---|
| mensgebonden-onderzoek@rivm.nl | |
| Website | http://www.rivm.nl/en/ |
"ROR" |
https://ror.org/01cesdt21 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Dutch Ministry of Health, Welfare and Sport, VWS
- Location
- Netherlands
Results and Publications
| Intention to publish date | 01/09/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Editorial Notes
19/12/2024: The overall end date was changed from 01/11/2024 to 26/11/2024.
12/08/2024: The following changes were made to the trial record:
1. The recruitment end date was changed from 29/04/2024 to 18/07/2024.
2. The total final enrolment was added.
30/01/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 29/01/2024 to 29/04/2024.
2. The overall study end date was changed from 01/09/2024 to 01/11/2024.
3. The inclusion criteria were updated.
05/12/2023: Contact details updated. The recruitment end date was changed from 04/12/2023 to 29/01/2024.
09/11/2023: The recruitment start date was changed from 18/09/2023 to 09/10/2023.
01/11/2023: Ethics approval reference added.
15/09/2023: Study's existence confirmed by the Dutch Medical Ethics Committee MEC-U.
